Heavy metals are widely dispersed in the environment and tend to accumulate in select tissues of the human body resulting in potential toxicity. They have also been reported to form complexes with certain classes of drugs, which may affect the availability, and consequently the activity of such drugs.High levels of heavy metals in environmental and food samples around Zaria, Nigeria have been reported. Hence, this study determined the concentrations of Cd, Cr, Mn, and Zn in blood of humans in Zaria and their effects on the availability and activity of chloramphenicol, ciprofloxacin and metronidazole. Results obtained show higher levels of the metals in occupationally exposed individuals compared to the general population. The in vitro availability of chloramphenicol, ciprofloxacin and metronidazole were significantly (P > 0.05) decreased when interacted with all the metals. The antimicrobial actions of chloramphenicol and metronidazole when interacted with the metals indicated that in most cases, the activity of the drugs was either antagonized or completely abolished. With ciprofloxacin however, synergistic changes in the zones of inhibition were generally observed in all cases.